Syphilis Update. roadmap

Transcription

1 AND Nurse Practitioners!!! AND Physician Assistants!!! Oliver Bacon, MD, MPH Physician, SF City Clinic Disease Prevention and Control Branch Population Health Division roadmap 1. Syphilis: diagnosis and treatment of 1ary, 2ary, Latent 2. Infectivity and partner services 3. Diagnostic challenges: window periods, titers, new algorithms 4. Approach to possible Neurosyphilis, including eyes and ears 5. Preventing congenital syphilis 2 1

2 Some Syphilis Basics Treponema Pallidum: motile (bendy) coiled spirochete with 6-14 spirals 6-15 um long, 0.24uM wide, non-gram staining: invisible on light microscopy Humans only host Cannot be cultured; no commercially available antigen/pcr testing Diagnosis: clinical, direct visualization by darkfield microscopy or immune fluorescence, plus serology Primary pathologic lesion: obliterative endarteritis with inflammatory infiltrate (plasma cells, macrophages, lymphocytes, +/- granulomas Systemic dissemination within 24 hours of inoculation Rapidly killed by penicillin, doxycycline

3 5 Primary, secondary syphilis: how it s supposed to happen: 1. See a typical lesion of primary or secondary syphilis 2. Confirm diagnosis with positive nontreponemal, treponemal serology, and direct visualization (darkfield or fluorescent microscopy rarely available) or tissue staining (impractical) 3. Treat (penicillin or doxycycline) But it s often not so straightforward.. 6 3

4 Case 1: 35, MSM, HIV(-), PrEP 11/1/17: PrEP quarterly follow-up at Magnet: RPR non-reactive 1/10/18: 2 small, dry sores on penis 1/17/18: Comes to City Clinic. STAT RPR, automated RPR, TPPA all negative 1/22/18: dermatologist. this is syphilis, and gives doxycycline 100mg BID x 14d 1/22/18: returns to City Clinic: STAT RPR nonreactive; automated RPR 1:2, TP-PA reactive: given benzathine Penicillin 2.4MU IM 7 What s going on here? 1. Secondary syphilis with a low titer RPR 2. Early latent syphilis: the penile lesions are something else 3. Primary syphilis in the serologic window period 4. Yaws 8 4

5 Serologic Syphilis Screening/Testing Paradigm TRADITIONAL Non-treponemal (NTT) tests (i.e., RPR, VDRL) Non-specific to TP Quantitative: reported as titer (1:1, 1:2, 1:4, 1:8, 1:16, 1:32 1:2048 and higher) Reactivity increases, then declines with time (usually highest in secondary) Susceptible to prozone phenomenon (usually in secondary) If NTT (+), reflex to: With treatment, some revert to nonreactive, others to low-reactive (serofast) Treponemal tests (i.e., TPPA, FTA-Abs) Specific to TP Qualitative Reactivity persists over time Timeline and infectivity: early through late disease STAGE STARTS LASTS (untreated) Other sxs Infectivity Primary 10d-12 weeks after inoculation (median time 21 d) Secondary 2-8 weeks after chancre heals or 4-8 weeks after onset of chancre can overlap with 1ary Early Latent After resolution of 2ary symptoms 1-6 weeks Papule->Chancre Nontender regional adenopathy Several weeks symmetric, bilateral rash mucous patches/condyloma lata fever, headache, pharyngitis hepatitis, osteitis, glomerulonephritis meningitis/ocular/oto- Until 1 year after inoculation can alternate with 2ary Late Latent 1 year after inoculation Until treatment or development of late symptomatic disease Late Symptomatic years after inoculation Neurologic: meningitis, ocular, oto-, meningovascular (strokes) Until treatment General paresis (CNS parenchyma) Tabes dorsalis (posterior columns: sensory/proprio) Cardiac (aortitis, infarction) Late benign (gummatous) Infectious by direct contact or blood Infectious by direct contact (when mucosal lesions present) or blood Infectious by direct contact (when mucosal lesions present) or blood Infectious by blood 10 5

6 Partner Services by SFDPH For Patients with syphilis When you partner with us, you help your partners. For patients with HIV or syphilis When you partner with us, you help your partners. Who are we? We re highly trained specialists who work at San Francisco City Clinic, with the Department of Public Health. What do we do? We help improve the health of people in San Francisco by partnering with Magnet. Why do we do it? HIV and Syphilis rates are high, especially among gay men. People who may have been exposed to HIV should get tested. Anyone exposed to syphilis should get both testing and treatment. Syphilis can be cured, but without treatment it can spread and cause serious health consequences. HIV can be managed, but unless people are tested and know their status, they may not get the care important to keeping them healthy. Offered to all patients with a new P&S syphilis diagnosis Offered to patients with new HIV infection Voluntary, culturally appropriate services How do we do it? In a CONFIDENTIAL, RESPECTFUL, and NONJUDGMENTAL conversation, we ll Make sure you receive the best care and treatment. Answer your questions. Help you figure out which of your sex partners may have been exposed and discuss the best ways to get them tested and/or treated. Help you contact your partners or, if you d like, contact them anonymously for you. Ask you some questions to help us better understand patterns of syphilis and HIV infection in San Francisco. When and where do We ll call you within a few days. we do it? We d like to meet in person or talk on the phone at a time that works for you. So that s us. What Talking with us is your choice. We hope you ll partner with us about you? to stop the spread of syphilis and HIV in. Got questions about Call us at (415) what we do? Got questions about HIV or syphilis? Check out or call us at (415) Primary Syphilis Textbook cases Painless ulcer at site of inoculation (unless superinfected) Usually indurated edges Darkfield positive (if darkfield microscopy available) Serology often, but not always, reactive Photos courtesy of Joe Engelman, MD, SF City Clinic 13 6

7 Primary Syphilis and HIV+ Multiple Ulcers, Atypical presentation San Francisco City Clinic Photos courtesy of Joe Engelman, MD, SF City Clinic 14 Primary syphilis- Chancres anywhere Raguse et al. Ann Int Med March

8 How often is the RPR negative in primary syphilis? 1) 5% of the time 2) 10% of the time 3) 20% of the time 4) 30% of the time 16 Performance of syphilis serologic tests Sena, CID 2010 Sena, CID

9 Secondary Syphilis Images courtesy of Joe Engelman City Clinic 18 Early latent syphilis 1. Positive, confirmed serology (NTT and Treponemal) AND 2. No signs of 1ary, 2ary disease AND 3. Evidence of infection with syphilis within the last year (any of the following): 4-fold or greater rise in nontreponemal titer History indicative of infection/exposure in the last year: Unequivocal symptoms of 1ary or 2ary syphilis in the prior year A sex partner within the prior year documented to have 1ary, 2ary, or early latent syphilis Late Latent or Latent of Unknown Duration: 1. Positive, confirmed serology (NTT and Treponemal) AND 2. No signs of 1ary, 2ary disease AND 3. No evidence of infection with syphilis within the last year If negative titer>1 year ago: late latent If no prior titer: Latent of unknown duration 19 9

10 Early Syphilis Treatment Primary, Secondary & Early Latent: Benzathine penicillin G 2.4 million units IM in a single dose Only one dose of PCN is recommended for early syphilis in HIV-infected persons, extra doses not needed 20 Staging determines Treatment If you cannot ascertain that infection was acquired in the prior year, then must treat for late disease What can help pinpoint timing of infection? Signs or symptoms of primary or secondary Can recall those symptoms in past year Contact to a known case in past year Negative syphilis test in the past year In HIV-infected patients, consider getting syphilis test with every CD4 or VL, approx every 3-6 months 21 10

11 Syphilis Treatment Primary, Secondary & Early Latent: Benzathine penicillin G 2.4 million units IM in a single dose Late Latent and Unknown Duration: Benzathine Penicillin G 7.2 million units total, given as 3 doses of 2.4 million units each at 1 week intervals Neurosyphilis: Aqueous Crystalline Penicillin G million units IV daily administered as 3-4 million IV q 4 hr for d Only one dose of PCN is recommended for early syphilis in HIV-infected persons, extra doses not needed 22 Follow-up/determining response to treatment: Repeat nontreponemal titer at (3), 6, (9), 12, (24) months (#)= HIV+, or patient at high risk of reinfection Serologic Rx failure: confirmed failure to achieve 4-fold decline in titer at 12 mo.; sustained 4-fold rise in titer in absence of repeat infection The NON-treponemal titer of many, but not all, patients treated for early syphilis will revert to zero. Some patients will achieve a 4-fold drop in titer, but remain NTT-reactive (serofast). It has been observed that serofast titers can be higher in some HIV(+) vs. HIV(-) patients. Please draw day-of-treatment titer (to establish a baseline) as they can fluctuate widely and quickly early in disease!! 11

12 Slow response or non-response: 15-27% of patients with early syphilis fail to achieve a fourfold decline in titer after 12 months, irrespective of HIV-infection status Declines are slower for late vs. early syphilis; and in patients with a prior history of syphilis May be slower in HIV-infected patients, esp. if NOT on ART or low CD4 If inadequate response is confirmed: CSF to look for neurosyphilis If(+): treat If (-): 3 weekly doses of 2.4MU benzathine PCN, and stop Sena CID 2011; Sena CID 2013; Ghanem K. CID 2008; Horberg M. STD 2010; Knaute DF CID 2012; CDC STD Treatment Guidelines MMWR Participants in US HIV Natural History Study (NHS) from Jan August 2013 Retrospective cohort study 478 syphilis cases 141 (29%) received 1 dose 253 (53%) received 2 doses 85 (18%) received other Ganesan CID

13 Ganesan CID Case No yo male, HIV+ Well-controlled on ART CD4 451 cells/µl VL undetectable Presents to clinic with 1 week history of rash on chest, back Papular, nonpruritic, hyperpigmented Spares the palms & soles AND (when you ask about it). Intermittent headache Blurry vision, especially at night Occasional flashing lights 27 13

14 Sexual history MSM, insertive/receptive oral & anal exposure Reports 10 partners in past year Location-based dating app with seroadaptive search strategy 28 Case 2, cont d: Additional history 3 weeks of intermittent headache blurry vision, esp. at night occasional flashing lights RPR 1:128 TP-PA reactive 29 14

15 What would you like to do? Audience Response Question: 1. Benzathine penicillin 2.4 MU 2. Obtain CSF 3. Refer urgently to ophthalmology 4. Notify partner services 5. All of the above 6. (1), (3), and (4) 30 CSF: WBC 4, Protein 41, glucose 65, CSF-VDRL nonreactive Referred to ophthalmologist for funduscopic examination Ophthalmologic exam reveals anterior uveitis both eyes left fundus: hyperemia, retinal inflammation, vasculitis 31 15

16 Syphilis When to LP? Clinical signs of neurosyphilis Cranial nerve dysfunction, meningitis, stroke, acute or chronic altered mental status, auditory or ophthalmic abnormalities (Ocular and Oto-syphilis ARE neurosyphilis) Confirmed serologic treatment failure Evidence of active tertiary syphilis (e.g. aortitis and gumma) HIV positive and late latent syphilis or syphilis of unknown duration: CSF does not seem to change outcome [REF: Marra] 32 Ocular Syphilis: occurs at any stage of syphilis Clinicians should be on the alert for ocular syphilis => delays in diagnosis have been associated with visual loss* Order syphilis serology test in patients with: visual complaints who have risk factors for syphilis or ophthalmologic findings compatible with syphilis order both treponemal and nontreponemal tests as prozone effect has been noted in patients with ocular syphilis Ask patients with syphilis about changes in their vision Patients with positive syphilis serology and visual complaints should receive immediate ophthalmologic evaluation *Moradi Am J Ophthal

17 Ocular Syphilis Manifestations: Conjunctivitis, scleritis, and episcleritis Uveitis: anterior and/or posterior Elevated intraocular pressure Chorioretinitis, retinitis Vasculitis Symptoms: Redness Eye pain Floaters Flashing lights Visual acuity loss Blindness Diagnosis: Ophthalmologic exam Serologies: RPR, VDRL, treponemal tests Lumbar puncture Slide courtesy of Sarah Lewis, MD Wender, JD et al. How to Recognize Ocular Syphilis. Review of Ophthalmology

18 Ocular Syphilis Management Patients with suspected ocular syphilis should receive a lumbar puncture and be treated for neurosyphilis CSF may be normal, but obtain to help guide follow-up Note: a negative LP does not rule out ocular syphilis Treatment for ocular syphilis is IV PCN (neurosyphilis regimen) even if the CSF lab tests are negative HIV test if not already known to be HIV-infected Report cases of ocular syphilis to the local health department within 1 business day. TREAT IN COLLABORATION WITH OPHTHALMOLOGIST! 36 Otosyphilis: occurs at any stage of syphilis Diagnosis: (+) serology with clinical evidence of infection of the cochleovestibular system with T. pallidum including: Sensorineural hearing loss (sudden or fluctuating) Tinnitus (often precedes hearing loss) Vertigo (sudden or fluctuating) May include osteitis of temporal bone role for imaging? 2017 Workowski, Sosa, Kidd. National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Yimtae et al. Otolaryngology Head and Neck Surgery (2007) 136, No other source of symptoms Consult with ENT for audiometry, co-management CSF may be normal, but obtain to help guide follow-up 37 18

19 Case 3 One of your new primary care patients is a 35 year old HIV positive woman who says she is taking antiretroviral therapy (Genvoya) and has an undetectable HIV RNA. She just moved here from out of state At her initial visit, you obtain baseline labs. Her pregnancy test is positive, and she wants to keep her pregnancy. The lab tells you that they have a new protocol for syphilis screening they are using treponemal EIA as the screening test Your patient s results: EIA positive, RPR negative. Now what? 39 Case 3: What to do next? 1) 1) Treat with one dose of 2.4 MU of Benzathine Penicillin IM 2) 2) Treat with three weekly doses of 2.4 MU of Benzathine Penicillin IM 3) 3) Tell her you would like to schedule an LP to rule out neurosyphilis, prior to deciding about treatment course 4) 4) Obtain another syphilis test 5) 5) Do nothing further as this is unlikely active syphilis 40 19

20 Syphilis Screening Paradigm TRADITIONAL Non-treponemal tests (i.e., RPR, VDRL) Non-specific to TP Quantitative Reactivity declines with time reflex to Treponemal tests (i.e., TPPA, FTA-Abs) Specific to TP Qualitative Reactivity persists over time Treponemal EIA/CIA Tests Reduce time and labor required for screening If positive, need quantitative RPR/VDRL for confirmation and to guide clinical management Remain detectable for life, even after successful treatment Limited utility as a screening test in previously treated patients 42 20

21 Reverse Sequence Syphilis Screening: Screening with Treponemal Immunoassay Negative Not Syphilis EIA or CIA Negative Positive Non-trep test (RPR) Positive Negative 2 nd Trep Test Positive Syphilis (past or present) 1) Unconfirmed EIA Unlikely syphilis; if pt at risk retest in 1 month Syphilis (past or present) APHL-CDC Consultation Report, 1/2009 MMWR 2011/Vol 60 (5) 43 Back to the patient You order a TPPA which comes back positive (EIA +, RPR-, TPPA+) You perform a thorough physical exam and do not detect any signs of syphilis The patient reports no prior history of syphilis and no known syphilis contacts in last year CD4 456, VL <

22 Case 3 What now? 1) 1. Treat with one dose of 2.4 MU benzathine penicillin 2) 2. Treat with three weekly doses of 2.4 MU benzathine penicillin 3) 3. Repeat syphilis testing in the 3 rd trimester, using the traditional testing algorithm, and again at delivery 4) 4. call partner services to help identify and test her partners 5) 5. perform NON-treponemal test (RPR or VDRL, whichever was used to test the mother on neonatal blood (NOT cord blood) at delivery. 6) 6. (2), (3), (4) and (5) 46 Test in 1 st trimester Repeat test in 3 rd trimester if increased risk of infection* If (+), staging determines treatment If late latent or unknown duration: no missed doses of benzathine PCN are acceptable. Restart 3-dose series. Benzathine PCN the ONLY treatment. If early syphilis, consider 2 nd dose of benzathine PCN 1 week after initial dose If PCN-allergy, desensitize and give benzathine PCN See CDC STD Guidelines for very detailed recommendations for allergy testing and desensitization (links below) For women diagnosed during pregnancy, in addition to treatment: Jarisch-Herxheimer reaction may cause premature labor, fetal distress, but not a reason to withhold treatment Any woman who delivers a stillborn infant should be tested *SF Screening criteria for syphilis: MSM; pregnancy; Transwomen; Trans-MSM Pregnancy Substance use; hx of syphilis; hx of incarceration; partner who is MSM; sex work; intimate partner violence 47 22

23 Thanks!! 48 Extra slides 49 23

24 50 Differential diagnosis of a genital ulcer Infection Syphilis HSV-2 or HSV-1 Pyogenic Chancroid LGV Donvanosis Traumatic Mechanical Chemical Allergic & Autoimmune Fixed drug eruption Behcets Disease Stevens-Johnson Reactive Arthritis Aphthous ulcers 51 24